Proteins are normally responsible for vital functions by forming specific native structures through folding. On the other hand, proteins may be misfolded to undergo aggregation into fibrils (amyloid fibril formation) rich in β-sheet structures. Aggregates (oligomers, protofibrils, and fibrils) produced in the course of this amyloid fibril formation are known to cause various dysfunctions (such diseases are collectively referred to as “amyloid diseases”), and 20 or more types of proteins have been identified as causative agents of the amyloid diseases. For example, amyloid β and Tau protein for Alzheimer's disease, α-synuclein for Parkinson's disease, amylin for diabetes mellitus, transthyretin for systemic amyloidosis, and huntingtin for Huntington's disease are known as such amyloids.
For example, as for amyloid β (abbreviated to Aβ), which is a causative amyloid of Alzheimer's disease, inhibitors of enzymes mediating the production of Aβ from a precursor protein, promoters of Aβ-degrading enzymes, immunotherapy, Aβ aggregation inhibitors, and the like are known as strategies to develop therapeutic drugs targeting these pathogenic amyloids.
On the other hand, it has been reported as to Aβ that a Met-oxidized form of an Aβ peptide (the sulfur atom of the Met residue is oxidized to sulfoxide (—S═O—)) remains in a small amount in vivo, and the Met-oxidized form is less aggregable as compared with the native Aβ peptide (Non Patent Literatures 1 to 3). From these viewpoints, the present inventors reported that oxidized forms of Aβ peptides are obtained by the oxidation of the Aβ peptides using a flavin photocatalyst having an Aβ-binding site represented by the formula (a), and these oxidized forms of Aβ peptides suppress the aggregation of Aβ (Non Patent Literature 4).
